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4q9n
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<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4q9n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4q9n OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4q9n RCSB], [http://www.ebi.ac.uk/pdbsum/4q9n PDBsum]</span></td></tr> | <tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4q9n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4q9n OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4q9n RCSB], [http://www.ebi.ac.uk/pdbsum/4q9n PDBsum]</span></td></tr> | ||
<table> | <table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The major phospholipid classes of the obligate intracellular bacterial parasite Chlamydia trachomatis are the same as its eukaryotic host except that they also contain chlamydia-made branched-chain fatty acids in the 2-position. Genomic analysis predicts that C. trachomatis is capable of type II fatty acid synthesis (FASII). AFN-1252 was deployed as a chemical tool to specifically inhibit the enoyl-acyl carrier protein reductase (FabI) of C. trachomatis to determine whether chlamydial FASII is essential for replication within the host. The C. trachomatis FabI (CtFabI) is a homotetramer and exhibited typical FabI kinetics, and its expression complemented an Escherichia coli fabI(Ts) strain. AFN-1252 inhibited CtFabI by binding to the FabI.NADH complex with an IC50 of 0.9 mum at saturating substrate concentration. The x-ray crystal structure of the CtFabI.NADH.AFN-1252 ternary complex revealed the specific interactions between the drug, protein, and cofactor within the substrate binding site. AFN-1252 treatment of C. trachomatis-infected HeLa cells at any point in the infectious cycle caused a decrease in infectious titers that correlated with a decrease in branched-chain fatty acid biosynthesis. AFN-1252 treatment at the time of infection prevented the first cell division of C. trachomatis, although the cell morphology suggested differentiation into a metabolically active reticulate body. These results demonstrate that FASII activity is essential for C. trachomatis proliferation within its eukaryotic host and validate CtFabI as a therapeutic target against C. trachomatis. | ||
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| + | Type II Fatty Acid Synthesis Is Essential for the Replication of Chlamydia trachomatis.,Yao J, Abdelrahman YM, Robertson RM, Cox JV, Belland RJ, White SW, Rock CO J Biol Chem. 2014 Aug 8;289(32):22365-76. doi: 10.1074/jbc.M114.584185. Epub 2014, Jun 23. PMID:24958721<ref>PMID:24958721</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Revision as of 05:36, 27 August 2014
Crystal structure of Chlamydia trachomatis enoyl-ACP reductase (FabI) in complex with NADH and AFN-1252
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